ArticleFrontiers in immunology2018
Toll-Like Receptors Drive Specific Patterns of Tolerance and Training on Restimulation of Macrophages.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis.International urogynecology journal · 2024Pooled it
- Fetal sex shapes placental inflammatory responses to extracellular mitochondrial DNA.bioRxiv : the preprint server for biology · 2026Article
- Macrophages as tissue scavengers, builders, and sensors.Function (Oxford, England) · 2026Review
- Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms.Frontiers in immunology · 2026Review
- Gut dysbiosis, metabolic signals, and pulmonary immune reprogramming: decoding the gut microbiota -immune axis in stroke-associated pneumonia.Frontiers in immunology · 2026Review
- Endotoxin Tolerance Impinges on T Cell Activation and Chemoattraction in Autoimmune Diabetes.Journal of immunology research · 2026Article
- Transcriptomic, Redox Status and Adipocytokine Profiles in Metabolic Dysfunction-Associated Steatotic Liver Disease: Impact of Coexisting Type 2 Diabetes.Medical sciences (Basel, Switzerland) · 2025Article
- Gut bacteriophages induce specific-reprogramming of macrophages to generate a protective innate immunity response to lipopolysaccharide exposure.Gut microbes · 2025Article
- Exploring Functionally Enhanced BLP-Trained Macrophage Subpopulations in S. Aureus Infection: Underlying Mechanisms and Therapeutic Significance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries.Nature communications · 2025Article
- Comparative analysis of isoproterenol- and lipopolysaccharide-mediated cytoprotective responses in the heart.American journal of physiology. Heart and circulatory physiology · 2025Article
- Toll-like receptor 4 induces trained innate immune tolerance in the heart in a model of stress-induced cardiomyopathy.Cardiovascular research · 2025Article
- Macrophage memory emerges from coordinated transcription factor and chromatin dynamics.Cell systems · 2025Article
- Innate Immune Memory is Stimulus Specific.bioRxiv : the preprint server for biology · 2025Article
- MnTheranostics · 2025Article
- Staphylococcus epidermidis alters macrophage polarization and phagocytic uptake by extracellular DNA release in vitro.NPJ biofilms and microbiomes · 2024Article
- Acute and persistent responses after H5N1 vaccination in humans.Cell reports · 2024Article
- Human milk affects TLR4 activation and LPS-induced inflammatory cytokine expression in Caco-2 intestinal epithelial cells.Scientific reports · 2024Article
- Microbiota and Immunity during Respiratory Infections: Lung and Gut Affair.International journal of molecular sciences · 2024Review
- Bacteria- and fungus-derived PAMPs induce innate immune memory via similar functional, metabolic, and transcriptional adaptations.Journal of leukocyte biology · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Tolerance is a long-recognized property of macrophages that leads to an altered response to repeated or chronic exposure to endotoxin. The physiological role of tolerance is to limit the potential damage to host tissue that may otherwise result from prolonged production of pro-inflammatory cytokines. Tolerance is induced by all toll-like receptor (TLR) ligands tested to date, however, tolerance induced by the TLR4 ligand lipopolysaccharide (LPS) is by far the best studied. LPS tolerance involves a global transcriptional shift from a pro-inflammatory response toward one characterized by the expression of anti-inflammatory and pro-resolution factors. Although largely reversible, LPS-tolerance leads to a hybrid macrophage activation state that is pro-inflammatory in nature, but possesses distinct regulatory anti-inflammatory features. Remarkably, a comparative transcriptomic analysis of tolerance induced by different TLR ligands has not previously been reported. Here, we describe the transcriptomic profiles of mouse macrophages tolerized with ligands for TLR2, TLR3, TLR4 and TLR 9. While we identified TLR-specific transcriptional profiles in macrophages tolerized with each ligand, tolerance induced by TLR4 represented an archetype pattern, such that each gene tolerized by any of the TLRs tested was also found to be tolerized by TLR4. Pro-inflammatory cytokines are not universally suppressed in all tolerant cells, but distinct patterns of cytokine expression distinguished TLR-specific tolerance. Analysis of gene regulatory regions revealed specific DNA sequence motifs associated with distinct states of TLR tolerance, implicating previously identified as well as novel transcriptional regulators of tolerance in macrophages. These data provide a basis for the future exploitation of TLR-specific tolerant states to achieve therapeutic re-programming of the innate immune response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.